Category: 860624-88-0

On December 13, 2018, Kerns, Jeffrey K.; Busch-Petersen, Jakob; Fu, Wei; Boehm, Jeffrey C.; Nie, Hong; Muratore, Michael; Bullion, Ann; Lin, Guoliang; Li, Huijie; Davis, Roderick; Lin, Xichen; Lakdawala, Ami S.; Cousins, Rick; Field, Rita; Payne, Jeremy; Miller, David D.; Bamborough, Paul; Christopher, John A.; Baldwin, Ian; Osborn, Ruth R.; Yonchuk, John; Webb, Edward; Rumsey, William L. published an article.Synthetic Route of 860624-88-0 The title of the article was 3,5-Disubstituted-indole-7-carboxamides as IKKβ Inhibitors: Optimization of Oral Activity via the C3 Substituent. And the article contained the following:

IκB kinase β (IKKβ or IKK2) is a key regulator of nuclear factor kappa B (NF-κB) and has received attention as a therapeutic target. Herein the authors report on the optimization of a series of 3,5-disubstituted-indole-7-carboxamides for oral activity. In doing so, the authors focused attention on potency, ligand efficiency (LE), and physicochem. properties and have identified compounds I and II as having robust in vivo activity. The experimental process involved the reaction of Methyl 5-bromoindoline-7-carboxylate(cas: 860624-88-0).Synthetic Route of 860624-88-0

The Article related to indolecarboxamide ikkbeta inhibitor, Pharmacology: Structure-Activity and other aspects.Synthetic Route of 860624-88-0

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On February 13, 2020, Na, Hyo Gyeong; Imran, Ali; Kim, Kyuneun; Han, Hong Sik; Lee, Young Jin; Kim, Myung-Jin; Yun, Chang-Soo; Jung, Young-Sik; Lee, Joo-Youn; Han, Soo Bong published an article.Name: Methyl 5-bromoindoline-7-carboxylate The title of the article was Discovery of a New Sulfonamide Hepatitis B Capsid Assembly Modulator. And the article contained the following:

Hepatitis B virus (HBV) remains a major health concern with 260 million people having been infected globally, and approx. 680,000 deaths have occurred annually from cirrhosis and liver cancer. The modulation of HBV capsid assembly has emerged as a promising therapeutic approach for curing chronic HBV infection. Small-mol. capsid assembly modulators (CAMs) can broadly be classified as heteroaryldihydropyrimidines and sulfamoylbenzamides (SBAs). SBAs are capsid activators that inhibit viral replication by achieving capsid assembly before polymerase encapsulation. Herein, we report a novel series of HBV CAMs based on NVR 3-778, a potent CAM belonging to the SBA class. The lead compound (KR-26556) exhibited improved pharmacol. activity and was examined through mol. docking studies. The experimental process involved the reaction of Methyl 5-bromoindoline-7-carboxylate(cas: 860624-88-0).Name: Methyl 5-bromoindoline-7-carboxylate

The Article related to hepatitis b capsid assembly antihbv mol docking studies, Pharmacology: Effects Of Antimicrobials and Parasiticides and other aspects.Name: Methyl 5-bromoindoline-7-carboxylate

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On July 13, 2017, Song, Yuntao; Brdiges, Alexander James published a patent.SDS of cas: 860624-88-0 The title of the patent was Preparation of 2-anilino-4-heteroaryl pyrimidine compounds as selective EGFR tyrosine kinase inhibitors for treatment of cancer. And the patent contained the following:

The present invention provides compounds of formula I or a subgeneric structure or species thereof, or a pharmaceutically acceptable salt, ester, solvate, and/or prodrug thereof, and methods and compositions for treating or ameliorating abnormal cell proliferative disorders, such as cancer,. Compounds of formula I [wherein A is (un)substituted indol-1-yl, (un)substituted indol-3-yl, (un)substituted indazol-3-yl, etc.; R1 = H, F, Cl, OH, etc.; R2 = -OCF3, cyclopropyl, methoxy, etc.; R3 = C2-6 alkenyl-R7, C2-6alkynyl-R7, R7, etc; R7 = OH, C1-6alkoxy, oxetanyl, pyrrolidinyl, etc.; R10 = H, -CD3, C1-6alkyl, etc.; E1 and E2 independently = C-R1 or N with the proviso that E1 and E2 are not both N; E3 and Z are independently CH or N; Y = -C(O)-CHCH-aryl, -C(O)-CHCH-heteroaryl, -S(O)2-CHCH-aryl, etc.] or a stereoisomer or a pharmaceutically acceptable salt, solvate, ester, or prodrug thereof, are claimed and exemplified. Example compound II was prepared from a multistep procedure (preparation given). Candidate compounds of I were evaluated for inhibition of proliferation of PC-9 cells from which II demonstrated an IC50 value of 6.8 nM. The experimental process involved the reaction of Methyl 5-bromoindoline-7-carboxylate(cas: 860624-88-0).SDS of cas: 860624-88-0

The Article related to anilino heteroaryl pyrimidine compound preparation egfr kinase inhibitor cancer, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.SDS of cas: 860624-88-0

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On May 31, 2007, Kerns, Jeffrey K.; Busch-Petersen, Jakob; Li, Huijie; Boehm, Jeffrey Charles; Nie, Hong; Taggart, John J. published a patent.Application of 860624-88-0 The title of the patent was Preparation of indolecarboxamide derivatives as inhibitors of kinase activity. And the patent contained the following:

The title compounds with general formula I [wherein X = O, S, S(O), S(O)2, etc,; R1 = H, (un)substituted alkyl, haloalkyl, heterocycloalkyl, etc.; R2 = (un)substituted alkyl, aryl, cycloalkyl, etc.; R3 = independently OH, oxo, alkyl, or haloalkyl; m = 1-3] or pharmaceutically acceptable salts thereof were prepared for the treatment of disorders associated with inappropriate IKK2 activities. In particular, I can be used for the treatment and prevention of inflammatory and tissue repair disorders, including rheumatoid arthritis, asthma, and COPD. For example, compound II was prepared in a multi-step synthesis. II exhibited IKK2 inhibitory activity with pIC50 value of 4.6 in IKK2 assay. The experimental process involved the reaction of Methyl 5-bromoindoline-7-carboxylate(cas: 860624-88-0).Application of 860624-88-0

The Article related to preparation indolecarboxamide inhibitor kinase activity, treatment inflammatory tissue repair disorder human, Heterocyclic Compounds (One Hetero Atom): Indoles, Indolizines, Carbazoles, and Other Arenopyrroles and other aspects.Application of 860624-88-0

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On October 2, 2008, Boehm, Jeffrey Charles; Busch-Petersen, Jakob; Fu, Wei; Jin, Qi; Kerns, Jeffrey K.; Li, Huijie; Lin, Guoliang; Lin, Xichen; Neipp, Christopher E. published a patent.COA of Formula: C10H10BrNO2 The title of the patent was Preparation of indolecarboxamide derivatives for use as IKK2 inhibitors. And the patent contained the following:

Title compounds I [R1 = YZ; R2 = bicyclo group or (un)substituted heterocycloalkyl containing S, S(O), or SO2; R3 and R4 independently = H or F; Y = bond, alkylene, alkenylene, or alkynylene; Z = (un)substituted aryl or heteroaryl; m = 0 or 1; with provisions], and their pharmaceutically acceptable salts, are prepared and disclosed as IKK2 inhibitors. Thus, e.g., II was prepared by bromination of 1-(1,1-dimethylethyl) 7-Me 2,3-dihydro-1H-1,7-dicarboxylate (preparation given) followed by deprotection, oxidation, condensation with tetrahydro-4H-thiopyran-4-one, protection, oxidation, deprotection/hydrolysis, amidation with ammonia, and coupling with phenylboronic acid. Select I were evaluated in IKK2 assays and demonstrated a pIC50 of about 5.0 to about 8.5. I were disclosed as therapeutic agents for the inhibition of IKK2 and can be useful in the treatment of disorders associated with inappropriate IKK2 (also known as IKKβ) activity, such as rheumatoid arthritis, asthma, rhinitis, and chronic obstructive pulmonary disease. The experimental process involved the reaction of Methyl 5-bromoindoline-7-carboxylate(cas: 860624-88-0).COA of Formula: C10H10BrNO2

The Article related to indolecarboxamide derivative preparation ikk2 inhibitor rheumatoid arthritis asthma rhinitis, Heterocyclic Compounds (One Hetero Atom): Indoles, Indolizines, Carbazoles, and Other Arenopyrroles and other aspects.COA of Formula: C10H10BrNO2

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On July 28, 2005, Baldwin, Ian Robert; Bamborough, Paul; Christopher, John Andrew; Kerns, Jeffrey K.; Longstaff, Timothy; Miller, David Drysdale published a patent.Name: Methyl 5-bromoindoline-7-carboxylate The title of the patent was Preparation of 7-indolecarboxamides as IKK2 kinase inhibitors for the treatment of such as inflammatory and tissue repair disorders. And the patent contained the following:

Title compounds I [wherein R1, R2 = H, halo, alkylene, alkenylene, (hetero)aryl, etc., and salts, solvates, or physiol. functional derivatives thereof] were prepared as IKK2 kinase inhibitors. For instance, Pd-catalyzed coupling of Boc-protected bromide II (preparation given) with phenylboronic acid followed by deprotection with HCl gave 7-indolecarboxamide III. Most invented compounds were found to have activity >4.8 in the IKK2 assay, in which the degree of phosphorylation of GST-IκBα was measured as a ratio of specific 665 nm energy transfer signal to reference europium 620 nm signal. Therefore, I and their pharmaceutical compositions are useful in the treatment and prevention of disease states mediated by IKK2 mechanisms, including inflammatory and tissue repair disorders. The experimental process involved the reaction of Methyl 5-bromoindoline-7-carboxylate(cas: 860624-88-0).Name: Methyl 5-bromoindoline-7-carboxylate

The Article related to indolecarboxamide preparation ikk2 kinase inhibitor, treatment inflammatory tissue repair disorder indolecarboxamide preparation, Heterocyclic Compounds (One Hetero Atom): Indoles, Indolizines, Carbazoles, and Other Arenopyrroles and other aspects.Name: Methyl 5-bromoindoline-7-carboxylate

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On June 4, 2009, Deng, Jianghe; Kerns, Jeffrey K.; Jin, Qi; Lin, Guoliang; Lin, Xichen; Lindenmuth, Michael; Neipp, Christopher; Nie, Hong; Thomas, Sonia M.; Widdowson, Katherine L. published a patent.Safety of Methyl 5-bromoindoline-7-carboxylate The title of the patent was Preparation of novel indolecarboxamides as IKK2 inhibitors. And the patent contained the following:

The title compounds I [R1 = XYZ, tetrahydroisoquinolinyl, dihydroisoindolyl; X = (un)substituted Ph, heteroaryl, etc.; Y = a bond or alkylene; Z = NR4R5 or heterocycloalkyl; R2, R3 = H, F, Cl; R4 = H, alkyl (optionally substituted with one hydroxy or one methoxy group); R5 = H, heterocycloalkyl, alkoxy, etc.; U = a bond, alkylene or alkenylene; V = Ph, 5-6 membered heteroaryl, 5-7 membered heterocycloalkyl, etc.] which are inhibitors of IKK2 and can be useful in the treatment of disorders associated with inappropriate IKK2 (also known as IKKβ) activity, such as rheumatoid arthritis, asthma, and COPD (chronic obstructive pulmonary disease), were prepared E.g., a multi-step synthesis of II, starting from indoline, was given. Selected compounds I were tested for activity against IKK2 (data given for representative compounds I). The invention is further directed to pharmaceutical compositions comprising a compound I. The invention is still further directed to methods of inhibiting IKK2 activity and treatment of disorders associated therewith using a compound I or a pharmaceutical composition comprising a compound I. The experimental process involved the reaction of Methyl 5-bromoindoline-7-carboxylate(cas: 860624-88-0).Safety of Methyl 5-bromoindoline-7-carboxylate

The Article related to indolecarboxamide preparation ikk2 inhibitor antirheumatic antiasthmatic copd treatment, indole amide preparation ikk2 inhibitor antirheumatic antiasthmatic copd treatment and other aspects.Safety of Methyl 5-bromoindoline-7-carboxylate

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On January 11, 2007, Deng, Jianghe; Kerns, Jeffrey K.; Jin, Qi; Lin, Guoliang; Lin, Xichen; Lindenmuth, Michael; Neipp, Christopher E.; Nie, Hong; Thomas, Sonia M.; Widdowson, Katherine L. published a patent.Computed Properties of 860624-88-0 The title of the patent was Preparation of novel indolecarboxamides as IKK2 inhibitors. And the patent contained the following:

The title compounds I [R1 = XYZ, tetrahydroisoquinolinyl, dihydroisoindolyl; X = (un)substituted Ph, heteroaryl, etc.; Y = a bond or alkylene; Z = NR4R5 or heteroocycloalkyl; R2, R3 = H, F, Cl; R4 = H, alkyl (optionally substituted with one hydroxy or one methoxy group); R5 = H, heterocycloalkyl, alkoxy, etc.; U = a bond, alkylene or alkenylene; V = Ph, 5-6 membered heteroaryl, 5-7 membered heterocycloalkyl, etc.] which are inhibitors of IKK2 and can be useful in the treatment of disorders associated with inappropriate IKK2 (also known as IKKβ) activity, such as rheumatoid arthritis, asthma, and COPD (chronic obstructive pulmonary disease), were prepared E.g., a multi-step synthesis of II, starting from indoline, was given. Selected compounds I were tested for activity against IKK2 (data given for representative compounds I). The invention is further directed to pharmaceutical compositions comprising a compound I. The invention is still further directed to methods of inhibiting IKK2 activity and treatment of disorders associated therewith using a compound I or a pharmaceutical composition comprising a compound I. The experimental process involved the reaction of Methyl 5-bromoindoline-7-carboxylate(cas: 860624-88-0).Computed Properties of 860624-88-0

The Article related to indolecarboxamide preparation ikk2 inhibitor antirheumatic antiasthmatic copd treatment, indole amide preparation ikk2 inhibitor antirheumatic antiasthmatic copd treatment and other aspects.Computed Properties of 860624-88-0

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

On March 30, 2006, Kerns, Jeffrey K.; Lindenmuth, Michael; Lin, Xichen; Nie, Hong; Thomas, Sonia M. published a patent.Electric Literature of 860624-88-0 The title of the patent was Indole derivatives as IKK2 inhibitors and their preparations, pharmaceutical compositions, and use for treatment of diseases associated with inappropriate IKK2 activity such as rheumatoid arthritis, asthma and chronic obstructive pulmonary disease. And the patent contained the following:

The invention is directed to indole carboxamide derivatives of formula I. Compounds of formula I wherein R1 is H, halo or YZ; R2 and R3 are independently H, F or Cl; Y is a bond, C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene; Z is (un)substituted (hetero)aryl; U is a bond, C1-6 alkylene or C2-6 alkenylene; V is (un)substituted Ph, (un)substituted 5- or 6-membered heteroaryl, (un)substituted 5- to 7-membered heterocycloalkyl, (un)substituted C5-7 cycloalkyl or (un)substituted C5-7 cycloalkenyl; and their pharmaceutically acceptable salts, solvates, or polymorphs thereof are claimed in this invention. The compounds of the invention are inhibitors of IKK2 and can be useful in the treatment of disorders associated with inappropriate IKK2 (also known as IKKss) activity, such as rheumatoid arthritis, asthma, and COPD (chronic obstructive pulmonary disease). Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting IKK2 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention. Example compound II was prepared by N-Boc protection of indoline followed by acylation with Me chloroformate to give Me 1-(tert-butoxycarbonyl)indoline-7-carboxylate, which underwent bromination to give 5-bromo derivative, which was deprotected; the resulting Me 5-bromoindoline-7-carboxylate was dehydrated to give the Me 5-bromoindolecarboxylate, which upon hydrolysis gave the 5-bromo-7-indolecarboxylic acid, which underwent cross-coupling with phenylboronic acid; the resulting 5-phenylindole-7-carboxylic acid was converted to the corresponding indolecarboxamide, which underwent condensation with N-benzyl-4-piperidinone to give 3-(4-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-5-phenylindole-7-carboxamide, which was subjected to hydrogenation; the resulting 3-(4-piperidinyl)-5-phenylindole-7-carboxamide was sulfonylated with 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethanesulfonyl chloride to give 3-[1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethanesulfonyl]piperidin-4-yl]-5-methyl-1H-indole-7-carboxamide, which was reacted with to give compound II. Addnl. 315 example compounds were prepared by similar methods. All the invention compounds were evaluated for their IKK2 kinase inhibitory activity. From the IKK2 assay, it was determined that example compound II along with several other compounds have pIC50 values of 5.0 or greater. In the monocyte assay, most of the tested compound showed IC50 values or less than 10μM. The experimental process involved the reaction of Methyl 5-bromoindoline-7-carboxylate(cas: 860624-88-0).Electric Literature of 860624-88-0

The Article related to indole preparation pharmaceutical composition ikk2 inhibitor, ikk2 inhibitor treatment rheumatoid arthritis asthma copd indole preparation, treatment disease associated ikk2 indole preparation and other aspects.Electric Literature of 860624-88-0

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles